Residues 1 to 80 of the N-terminal domain of the β subunit confer neuronal bungarotoxin sensitivity and agonist selectivity on neuronal nicotinic receptors

AbstractStandard two electrode voltage clamp techniques were used to investigate the response of neuronal nicotinic acetylcholine receptors, expressed in Xenopus oocytes, to various agonists and neuronal bungarotoxin (NBT). The β subunit is an important determinant of the receptor's pharmacological profile. Co-expression of α4 and β2 subunits produced a receptor that was relatively insensitive to cytisine and nicotine and inhibited by NBT, whilst the α4β4 combination produced a receptor that was highly sensitive to cytisine and nicotine but resistant to toxin. The first 80 amino acids of the N-terminal domain of the β subunit are implicated in these characteristics, since the combination of α4 with a hybrid β subunit comprising amino acids 1 → 80 of β2 and 81 → 416 of β4 became relatively insensitive to nicotine and cytisine and resistant to inhibition by neuronal bungarotoxin